Despite advances, cardiovascular diseases (CVD), including ischemic heart disease (IHD), remain a significant public health threat. Unfortunately, our ability to predict who will develop IHD/CVD and who will die prematurely remains limited because many conventional diagnostic and interventional measures are designed to identify and treat obstructive coronary artery disease. A major challenge is prompt diagnosis and intervention for patients who have coronary microcirculation dysfunction without significant epicardial coronary stenosis. This limited ability to predict progression and outcomes is particularly harmful to women: women exhibit much lower levels of epicardial coronary stenosis, much higher rates of CV dysfunction induced by mental or psychosocial stressors, and are typically under-represented in cardiology studies. Thus, to reduce prevalence and improve outcomes, we must first better understand the mechanisms behind non-obstructive IHD in women. We and others have shown that mental stress testing in the laboratory provokes mental stress induced left ventricular dysfunction (MSILVD) in certain patients with IHD and is more common in women; others' work strongly suggests that MSILVD is also likely to be present in individuals without IHD. In our work, relative to conventional exercise stress testing, mental stress causes a greater left ventricular ejection fraction (LVEF) reduction, a variable has been consistently found to be linearly associated with increased risk of adverse CV outcomes in IHD patients. Our data also indicates mental stress induced LVEF change may be the strongest predictor for heart failure exacerbation requiring inpatient care. Growing evidence suggests that a mechanism that could be a key link between psychosocial or mental stress and CVD/IHD is mitochondrial dysfunction and mitochondrial dysfunction has been recently (Ashar2017) reported to be an independent risk factor for development and poor prognosis of IHD/CVD. We thus propose the first systematic study of mitochondrial (dys)function and MSILVD in women with various CV risk factors. The AIMS of the study include: 1) Determine the rates of MSILVD in three groups of women differing on CV risks (women with documented IHD, women without IHD but have ?2 CV risk factors, and age matched healthy women without CV risks). 2). a) Investigate the association between mitochondrial dysfunction and MSILVD status, and b) Delineate mitochondrial responses to mental stress testing in these women.. To accomplish the aims of this project, we will recruit 120 adult women in each of the following three groups: (1) those with documented IHD, (2) those with ?2 CV risk factors but no IHD, (3) those who are age matched to (2) but who have no CV risk factors and no clinically identified medical and/or psychiatric diseases. Our team is uniquely positioned to achieve these aims. If, as expected, we confirm an association between MSILVD, mitochondrial dysfunction, and IHD/CVD in women, our work may be used both to guide the development of novel therapeutic strategies and to improve identification of patients susceptible to developing IHD and other CVD who have low levels of stenosis.